The invention relates to proteins whose presence, absence, concentration in biological samples, or expression level can be used to indicate the presence or absence of tumors, cancer, and related conditions as well as related prognoses and diagnoses.
Tumors are abnormal masses of tissue. When tumors proliferate uncontrollably, they are said to become malignant. This condition is generally referred to as a cancer. Numerous methods are used to determine when a patient has developed a tumor and when the condition has become cancerous. The identification or quantitation of various tumor or cancer markers is one desirable means for making such determinations.
Broadly, a “marker” is any property that can be used to distinguish cancer from normal tissues and from other disease states. The markers' presence is then a basis for classification. More specifically, the term is used to denote particular molecules that are amenable to assay. Serum markers, as the name implies, are markers that are readily assayed in the serum of a patient. Typically, they are secreted proteins or cell receptors that are abundant in tumor cells well beyond their presence (or total absence) in normal cells and tissues. Examples include PSA, CEA, and AFP.
A more expansive consideration of tumor and cancer markers includes the detection of tumors and cancer from the nucleic acids produced in various cells (as well as other materials that are related to nucleic acids). Cancer is generally considered to be a disease of multiple mutations. Thus, detection of the mutations at the molecular level offers the prospect of more direct and more reliable diagnoses than was possible with some of the older cancer markers. Thus, it is appropriate to consider a nucleic acid sequence that is indicative of the mutation that causes or occurs with the cancerous condition to be a cancer marker. The ability to conduct nucleic acid analyses does not vitiate the value of serum markers, however. Each may have an appropriate role to play in the diagnosis, staging, and treatment monitoring of a patient.
Discovering genes that encode cancer-associated antigens and events also opens the door to genetic intervention against cancer cell proliferation. The accurate and consistent use of a cancer marker to differentiate cancerous from normal tissue, not only has diagnostic potential, but is also desirable for treatment and prognosis. Therefore, such markers continue to be sought.
The reg proteins, which belong to the C-type lectin superfamily, are secreted proteins of about 20 kD in size. They are found in normal and malignant tissues of the gastrointestinal tract, in the pituitary and in regenerating neurons. Reg expression associates with cell proliferation, migration and differentiation (Chiba T et al., 2000, J Gastroenterol 35 Suppl 12:52, Levine J L, 2000, Surg Res 89:60, Otonkoski T et al., 1994, Diabtets 43:1164, Bernard-Perronese FR, 1999, J Histochem Cytochem 47:863). The known reg genes cluster on human chromosome 2p12. The first characterized member of the reg protein family was Reg 1α, which was isolated from rat regenerating pancreatic islets (Terazono et al., 1988). Subsequently, cDNAs encoding for four additional human reg proteins, and the corresponding mouse and rat orthologs, have been cloned (Watanabe et al., 1990; Lasserre et al., 1992; Bartoli et al., 1993; Rafaeloff et al., 1997). They exert mitogenic activity to subsets of epithelial and neuroectodermal cells (Katsumata et al., 1995, Zenilman et al., 1996; 1997; 1998; Livesey et al., 1997). A growth signal transducing receptor for rat reg1 proteins was recently described. The receptor is encoded by a gene homologous to human multiple exostoses gene. It was found to have been expressed, in addition to pancreatic islets, in various tissues including kidney, liver, gut, the adrenal and pituitary glands (Kobayashi S et al. 2000).
Identification, isolation, and use of new tumor and cancer markers remain important in the diagnosis, treatment and prevention of cancer.